The proposed research would continue and extend studies on the transport and reaction processes involved in the disposition of I-131 insulin and related peptides, I-131 glucagon and I-131 proinsulin in the rat, with special emphasis on the role of the liver in insulin: glucose homeostasis and possible derangements in diabetes. The studies would be directed toward the development of difinitive mathematical models which would predict observed data and account for the physiological processes known or believed to occur. To these ends of kinetics, nature, sites, and specificity of the degradative and transport processes for I-131 insulin and related peptides and the relationships between membrane binding, biological activity, and degradation would be investigated in subcellular fractions of rat livers both in vivo and in vitro and extended to studies of livers of non-diabetic and diabetic human subjects. The models would ultimately be utilized to analyze curves of I-131 insulin plasma disappearance in non-diibetic and diabetic subjects of determine the specific causes that produce and influence the magnitudes and rates of change in plasma insulin levels following glucose administration in terms of dynamics, reaction rates, and insulin turnover. The approach to the proposed research would be interdisciplinary and would be coordinated with research grant application entitled, "Studies in the Dynamics of Physiological Systems", under the direction of Frederick Horn, Ph.D., Professor of Chemical Engineering, University of Rochester, as principal investigator, and Martin Feinberg, Ph.D., Assistance Professor of Chemical Engineering, as co-investigator, which is being submitted as a separate but coordinated application.